Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

Bivalent PROTACs work drive protein degradation by simultaneously binding a target protein and an E3 ligase and forming a productive ternary complex. We hypothesized that increasing binding valency within a PROTAC could enhanced degradation. Here, we designed trivalent PROTACs consisting of a bivalent BET inhibitor and an E3 ligand, tethered via a branched linker. We identified VHL-based SIM1 as a low picomolar BET degrader, with preference for BRD2. Compared to bivalent PROTACs, SIM1 showed more sustained and higher degradation efficacy, which led to more potent anti-cancer activity. Mechanistically, SIM1 simultaneously engages with high avidity both BET bromodomains in a cis intramolecular fashion and forms a 1:1:1 ternary complex with VHL exhibiting positive cooperativity and high cellular stability with prolonged residence time. Collectively, our data along with favorable in vivo pharmacokinetics demonstrate that augmenting the binding valency of proximity-induced modalities can be an enabling strategy for advancing functional outcomes.

Prejudice Towards Sex Workers Depends on the Sexual Activity and Autonomy of Their Work, Hobbies and Daily Activities

Women are more likely than men to be sexualized, objectified and dehumanized. Female sex workers experience stigma and violence associated with these judgements at far higher rates than other women. Here, we use a pre-registered experimental design to consider which aspects of sex work – the level of sexual activity, earned income, or perceived autonomy of the work – drive dehumanization. A first group of participants (N = 217) rated 80 vignettes of women varying by full-time employment, hobbies and interests on humanness. These ratings were subtracted from the ratings of a second group of participants (N = 774) who rated these same vignettes which additionally described a part-time job, hobby or activity that varied in sexual activity, income earned and autonomy over one’s actions. We find that women and especially men dehumanize women they believe are engaging in penetrative sex. We also find that women’s autonomy of, but not their income from, their sexual activity increases dehumanization. Our findings suggest that opposition to women’s ability to pursue casual sex and generalizations about the exploitative conditions of sex work may drive the harshest negative prejudice towards female sex workers and, by similar mechanisms, women’s sexuality in general.

Unravelling Work Drive: A Comparison between Workaholism and Overcommitment

Workaholism and overcommitment are often used as interchangeable constructs describing an individual’s over-involvement toward their own job. Employees with high levels in both constructs are characterized by an excessive effort and attachment to their job, with the incapability to detach from it and negative consequences in terms of poor health and job burnout. However, few studies have simultaneously measured both constructs, and their relationships are still not clear. In this study, we try to disentangle workaholism and overcommitment by comparing them with theoretically related contextual and personal antecedents, as well as their health consequences. We conducted a nonprobability mixed mode research design on 133 employees from different organizations in Italy using both self- and other-reported measures. To test our hypothesis that workaholism and overcommitment are related yet different constructs, we used partial correlations and regression analyses. The results confirm that these two constructs are related to each other, but also outline that overcommitment (and not workaholism) is uniquely related to job burnout, so that overcommitment rather than workaholism could represent the true negative aspect of work drive. Additionally, workaholism is more related to conscientiousness than overcommitment, while overcommitment shows a stronger relationship with neuroticism than workaholism. The theoretical implications are discussed.

Prejudice towards sex workers depends on the sexual activity and autonomy of their work, hobbies and daily activities

Women are more likely than men to be sexualized, objectified, and dehumanized. Female sex workers experience stigma and violence associated with these judgements at far higher rates than other women. Here, we use a pre-registered experimental design to consider which aspects of sex work – the level of sexual activity, earned income, or perceived autonomy of the work – drive dehumanization. A first group of participants (N = 217) rated 80 vignettes of women varying by full-time employment, hobbies and interests on humanness. These ratings were subtracted from the ratings of a second group of participants (N = 774) who rated these same vignettes which additionally described a part-time job, hobby or activity that varied in sexual activity, income earned and autonomy over one’s actions. We find that women and especially men dehumanize women they believe are engaging in penetrative sex. We also find that women’s autonomy of, but not their income from, their sexual activity increases dehumanization. Our findings suggest that opposition to women’s ability to pursue casual sex and generalizations about the exploitative conditions of sex work may drive the harshest negative prejudice towards female sex workers and, by similar mechanisms, women’s sexuality in general.

Aesthetic labour, class and taste: Mobility aspirations of middle-class women working in luxury-retail

Previous research has shown how the embodied performances expected from service workers make cultural class background important for entry into these forms of jobs. However, class judgement continues to impact the worker post-entry and on-the-job. We explore this through a qualitative study of 18 middle-class women working in luxury-retail stores in Amsterdam, asking how they acquire the taste of their store for aesthetic labour. This is a case we consider pertinent given the significant class difference between these workers and their economically rich clientele. We found that: (1) workers constructed the products they sold as distinct by devaluing ‘popular’ fashion products; (2) workers managed to acquire luxury knowledge through their work practices; (3) workers purchased luxury products via employee discount, the availability of which triggered allures to emulate their upper-class customers; (4) acquiring this taste was perceived as cultural-social mobility, a perception reinforced by feelings of recognition within private consumption practices; and (5) these endeavours were often marked by both avidity and anxiety, as work concerns conflated with class concerns. We conclude by arguing that systems of classification and the labour process work in alloy, as the necessities of work drive conformity to legitimate taste and, in turn, the legitimacy of taste assists in achieving worker motivation and the extraction of labour. This, we believe, reflects potential complementarity between domination and exploitation models of class analysis.

Medical Transcription a pioneer in the Healthcare Informatics

Despite the importance of medical records, relatively little is known about medical transcription, a process through which voice files are transformed into healthcare documentation. This lack of knowledge is evident in academic research with no previous studies of medical transcriptionists (MTs) or the medical transcription service organizations (MTSOs) in existence despite the central role of the industry in the creation of healthcare documentation. The proposed chapter is a detailed ethnographic study of the medical transcription process. While its general aim is to document the impact of technology on the process of medical transcription, the topic resides in a broader array of issues that include the impact of technology on the workplace, and how assumptions of work drive technological design. The central issue being examined is what is the extent to which technology can replace workers and how design decisions impact practice by either facilitating or impeding it. Given the thing being produced is vital for medical treatment, resolving this question is not only of academic interest, but important to everyone who has a medical record.

Moderators of the curvilinear relation between extent of telecommuting and job and life satisfaction: The role of performance outcome orientation and worker type

The purpose of this study is to determine factors that are related to employee satisfaction with telecommuting. Recent research supports the notion of a curvilinear relation between extent of telecommuting and job satisfaction. Drawing on control theory, we find that performance outcome orientation (degree to which objective criteria are used in employee evaluation) moderates the curvilinear relation between extent of telecommuting and job satisfaction. We also find support for a curvilinear (inverted U) relation between extent of telecommuting and life satisfaction, with worker type (defined by work drive and work enjoyment) moderating that relation.